The 60kD heat shock protein (hsp60) is a highly conserved protein and a dominant antigen of most pathogenic bacteria. In some women, chronic or repeated upper genital tract infections with Chlamydia trachomatis, and possibly with other microorganisms, induces immune sensitization to epitopes of hsp60 that are present in both the microbial and human hsp60. Once a woman becomes sensitized to these conserved epitopes, any subsequent induction of human or bacterial hsp60 expression will reactivate hsp60‐sensitized lymphocytes and initiate a pro‐inflammatory immune response. Hsp60 is expressed during the early stages of pregnancy, by both the embryo and the maternal decidua. We examined, therefore, whether women who were sensitized to hsp60 experienced less successful pregnancy outcomes compared to women who were not sensitized to this antigen. In women undergoing in vitro fertilization (IVF), the presence of cervical IgA antibodies reactive with the C. trachomatis hsp60 correlated with implantation failure after embryo transfer. Further analysis revealed that an immunodominant epitope for these IgA antibodies was an hsp60 epitope shared between C. trachomatis and man. In subsequent studies of women not undergoing IVF, cervical IgA antibodies to the human hsp60 were identified in 13 of 91 reproductive age women. This antibody was most prevalent in those women with a history of primary infertility (p = 0.003). In addition, cervical anti‐hsp60 IgA correlated with the detection of the pro‐inflammatory cytokines interferon‐γ (p = 0.001) and tumor necrosis factor‐α (p = 0.02) in the cervix. Conversely, women with proven fertility had the highest prevalence of the anti‐inflammatory cytokine, interleukin 10, in their cervices (p = 0.001). In an analysis of serum samples in a third study, women with a history of two or more consecutive first trimester spontaneous abortions had a higher prevalence (p = 0.01) of IgG antibodies to the human hsp60 (36.8%) than did age matched fertile women (11.1%) or women with primary infertility (11.8%). Immune sensitization to epitopes expressed by the human hsp60 may reduce the probability of a successful pregnancy outcome due to reactivation of hsp60‐reactive lymphocytes, induction of a pro‐inflammatory cytokine response and interference with early embryo development and/or implantation. © 1996 Wiley‐Liss, Inc.

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Pregnancy outcomes for 125 women with unexplained recurrent abortion conceiving after immunologic testing for possible paternal leukocyte immunization were analyzed. Pregnancy success was related to the number of previous miscarriages (relative risk 0.36 for each additional miscarriage after 3), a history of a late pregnancy loss (relative risk 0.18), any other relevant treated or untreatable diagnosis (relative risk 0.27), immunization with paternal mononuclear cells (relative risk 5.6), and time in weeks from test date to LMP of the next pregnancy (relative risk 0.93 for each additional week). The significant difference in pregnancy outcomes between women given a single immunization and nonimmunized women reflected a larger difference between those in each group conceiving within 12 weeks of initiating tests for inclusion in the treatment program. The latter observation suggests that any effect from a single immunization in prevention of recurrent miscarriage is of relatively short duration.